Related Experiment Video

Updated: Aug 4, 2026

Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
11:28

Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus

Published on: October 7, 2011

Lymphotoxins and cytomegalovirus cooperatively induce interferon-beta, establishing host-virus détente

C A Benedict1, T A Banks, L Senderowicz

  • 1Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.

Immunity
|October 24, 2001
PubMed

Insights

Lymphotoxin (LT) signaling inhibits cytomegalovirus (CMV) replication through interferon-beta (IFN-beta) induction. This host defense mechanism is crucial for controlling CMV infection, as demonstrated by increased susceptibility in LT-deficient mice.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Cytokines like tumor necrosis factor (TNF) regulate cell death and survival, influencing viral persistence.
  • Viruses such as cytomegalovirus (CMV) evolve counterstrategies to evade host immune responses.
  • Understanding host-pathogen interactions is key to controlling viral infections.

Purpose of the Study:

  • To investigate the role of lymphotoxin (LT) signaling in controlling cytomegalovirus (CMV) infection.
  • To elucidate the mechanism by which LT signaling inhibits viral replication.
  • To determine the necessity of LT signaling in host defense against CMV.

Main Methods:

  • Utilized cell culture models to study human CMV infection and replication.
  • Investigated signaling pathways involving lymphotoxin-beta receptor (LT-beta R) and TNF receptor-1.
  • Employed mouse models, including LT alpha-deficient and LT beta R-Fc transgenic mice, to assess susceptibility to murine CMV (mCMV) infection.
  • Analyzed the induction of interferon-beta (IFN-beta) via nuclear factor kappa B (NF-kappa B) signaling.

Main Results:

  • Lymphotoxin (LT)-beta receptor and TNF receptor-1 signaling, but not Fas or TRAIL receptors, inhibited human CMV replication and cytopathicity.
  • This inhibition occurred via a nonapoptotic, reversible process dependent on NF-kappa B-induced interferon-beta (IFN-beta).
  • Efficient IFN-beta induction required both viral infection and LT signaling, highlighting the interplay of host and viral factors.
  • LT alpha-deficient and LT beta R-Fc transgenic mice exhibited profound susceptibility to murine CMV (mCMV) infection.

Conclusions:

  • Lymphotoxin (LT) signaling plays an essential and conserved role in host defense against cytomegalovirus (CMV).
  • The LT-LT beta R pathway is critical for controlling viral replication without causing cell death.
  • This pathway, involving NF-kappa B and IFN-beta induction, represents a vital host defense mechanism against CMV persistence.

More Related Videos

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production08:32

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

Accessing Early Differentiation of Virus-Specific Follicular Helper CD4+ T Cell in Acute LCMV-Infected Mice05:03

Accessing Early Differentiation of Virus-Specific Follicular Helper CD4+ T Cell in Acute LCMV-Infected Mice

Published on: April 26, 2024

Related Concept Videos

Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
Viruses with RNA Genomes01:29

Viruses with RNA Genomes

RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
Cytomegalovirus Disease01:27

Cytomegalovirus Disease

Cytomegalovirus (CMV) disease is caused by human cytomegalovirus, a double-stranded DNA virus of the Herpesviridae family. While primary CMV infection is often asymptomatic in immunocompetent individuals, the virus can cause severe disease in neonates and immunocompromised patients. CMV is the most common cause of congenital viral infection in the United States, and a major pathogen in solid organ and hematopoietic stem cell transplant recipients.CMV is transmitted via bodily fluids, sexual...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
Inhibitors of Virion Maturation and Assembly01:19

Inhibitors of Virion Maturation and Assembly

As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...